Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-005)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01926509
First received: August 19, 2013
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

This study will evaluate the safety, tolerability, and PK of MK-8892 in participants with pulmonary arterial hypertension. The primary hypothesis is that the geometric mean of MK-8892 area under the concentration time-curve from Hour 0 to 24 hours (AUC0-24hr) in participants with PAH, will be equal to or greater than the efficacious exposure in humans of 0.6 μM•hr.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: MK-8892
Drug: Placebo for MK-8892
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 28-Day Multiple-Dose Titration Study to Assess the Effects of MK-8892 on Safety, Tolerability and Pharmacokinetics in Subjects With Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Area Under the Concentration Time-curve from Hour 0 to 24 hours (AUC0-24hr) of MK-8892 [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours postdose on Days 1 and 28 ] [ Designated as safety issue: No ]
  • Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event [ Time Frame: up to 28 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: November 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel A
Participants will be administered MK-8892 or matching placebo orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).
Drug: MK-8892 Drug: Placebo for MK-8892
Experimental: Panel B
Participants will be administered MK-8892 or matching placebo orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28)
Drug: MK-8892 Drug: Placebo for MK-8892
Experimental: Panel C
Participants will be administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 8 mg (Days 22-28).
Drug: MK-8892

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • If female, cannot be pregnant or breastfeeding. Females of reproductive potential must agree to agree to use (and/or have their partner use) two (2) acceptable methods of birth control throughout the study and until 2 weeks after the last dose of study drug is administered
  • Body mass index (BMI) ≤34 kg/m^2 and a total body weight >40 kg (>88 lbs)
  • Has Group 1 pulmonary hypertension (PAH) as defined by the Dana Point 2008 Clinical Classification including: idiopathic PAH (IPAH), Heritable PAH, Drug and toxin-induced PAH, PAH associated with connective tissue disease or congenital heart disease (repaired simple cardiac defects at least 1 year status post corrective surgery, with no residual intracardiac or extracardiac shunt)
  • On a stable regimen of background therapy for at least 3 months prior to starting study drug
  • Have history of right heart catheterization within two years demonstrating pulmonary arterial hypertension
  • Had pulmonary function testing within one year of starting study medication demonstrating total lung capacity (TLC) >70% predicted, forced expiratory volume in 1 second (FEV1) >70% predicted
  • Have hemoglobin >75% of the lower limit of the normal range

Exclusion Criteria:

  • Pulmonary hypertension subtypes including the following according to Dana Point 2008 Clinical Classification: human immunodeficiency virus (HIV) infection, portal hypertension, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn (PPHN), pulmonary hypertension due to left heart diseases such as systolic dysfunction, diastolic dysfunction or valvular disease, pulmonary hypertension due to lung diseases and/or hypoxia (e.g. chronic obstructive pulmonary disease, interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental abnormalities), chronic thromboembolic pulmonary hypertension (CTEPH), hematologic disorder (myeloproliferative disorders, splenectomy), systemic disorders (sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis), metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders) or other disorder (tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis)
  • Have secondary forms of pulmonary hypertension due to pulmonary veno-occlusive disease (PVOD), or pulmonary capillary hemangiomatosis (PCH)
  • Resting systolic blood pressure <105 mmHg, or resting heart rate ≥110/min
  • Family history of Long QT Syndrome
  • Uncorrected hypokalemia or hypomagnesemia
  • Taking medications that are potent inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4) including but not limited to cyclosporine, systemic itraconazole or ketoconazole, glyburide, erythromycin, clarithromycin, or telithromycin, nefazodone, protease inhibitors, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifampicin, St John's wort, diltiazem and verapamil) or has discontinued treatment <3 weeks prior to the start of the study. Concomitant medications, including anticoagulants, angiotensin converting enzyme (ACE) -inhibitors, diuretics, bosentan, ambrisentan and selected calcium channel blockers (e.g., amlodipine) may be allowed at the discretion of the investigator with the concurrence of the Sponsor.
  • Unable to refrain from or anticipates the use of organic nitrates (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol) beginning approximately 2 weeks before start of study and throughout the study
  • Unable to refrain from or anticipates the use of prostanoid therapies beginning approximately 2 weeks before start of study and throughout the study
  • Consume excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
  • Major surgery or donated blood within previous 8 weeks
  • Participated in another investigational study within 4 weeks
  • History of significant multiple and/or severe allergies
  • Regular user of illicit drugs, or has a history of drug (including alcohol) abuse, within approximately 6 months
  • Pregnant or breast-feeding, or expecting to conceive
  • Interstitial lung disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01926509

Contacts
Contact: Toll Free Number 1-888-577-8839

Locations
Bulgaria
Merck Sharp & Dohme Bulgaria EOOD Recruiting
Sofia, Bulgaria
Contact: Eran Gefen    38 (044) 393 74 80      
Germany
Merck Sharp & Dohme GmbH Recruiting
Haar, Germany
Contact: German Medical Information Center    49 800 673 673 673      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01926509     History of Changes
Other Study ID Numbers: 8892-005, 2013-002529-51
Study First Received: August 19, 2013
Last Updated: July 15, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 22, 2014